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A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice
Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682941/ https://www.ncbi.nlm.nih.gov/pubmed/26673420 http://dx.doi.org/10.1371/journal.pone.0144196 |
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author | Alves, Joana Madureira, Pedro Baltazar, Maria Teresa Barros, Leandro Oliveira, Liliana Dinis-Oliveira, Ricardo Jorge Andrade, Elva Bonifácio Ribeiro, Adília Vieira, Luís Mira Trieu-Cuot, Patrick Duarte, José Alberto Carvalho, Félix Ferreira, Paula |
author_facet | Alves, Joana Madureira, Pedro Baltazar, Maria Teresa Barros, Leandro Oliveira, Liliana Dinis-Oliveira, Ricardo Jorge Andrade, Elva Bonifácio Ribeiro, Adília Vieira, Luís Mira Trieu-Cuot, Patrick Duarte, José Alberto Carvalho, Félix Ferreira, Paula |
author_sort | Alves, Joana |
collection | PubMed |
description | Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases. |
format | Online Article Text |
id | pubmed-4682941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46829412015-12-31 A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice Alves, Joana Madureira, Pedro Baltazar, Maria Teresa Barros, Leandro Oliveira, Liliana Dinis-Oliveira, Ricardo Jorge Andrade, Elva Bonifácio Ribeiro, Adília Vieira, Luís Mira Trieu-Cuot, Patrick Duarte, José Alberto Carvalho, Félix Ferreira, Paula PLoS One Research Article Group B Streptococcus (GBS), a commensal organism, can turn into a life-threatening pathogen in neonates and elderly, or in adults with severe underlying diseases such as diabetes. We developed a vaccine targeting the GBS glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a glycolytic enzyme detected at the bacterial surface, which was proven to be effective in a neonatal mouse model of infection. Since this bacterium has emerged as an important pathogen in non-pregnant adults, here we investigated whether this vaccine also confers protection in an adult susceptible and in a diabetic mouse model of infection. For immunoprotection studies, sham or immunized adult mice were infected with GBS serotype Ia and V strains, the two most prevalent serotypes isolated in adults. Sham and vaccinated mice were also rendered diabetic and infected with a serotype V GBS strain. For toxicological (pre-clinical) studies, adult mice were vaccinated three times, with three concentrations of recombinant GAPDH adjuvanted with Allydrogel, and the toxicity parameters were evaluated twenty-four hours after the last immunization. For the stability tests, the vaccine formulations were maintained at 4°C for 6 and 12 months prior immunization. The results showed that all tested doses of the vaccine, including the stability study formulations, were immunogenic and that the vaccine was innocuous. The organs (brain, blood, heart, and liver) of vaccinated susceptible or diabetic adult mice were significantly less colonized compared to those of control mice. Altogether, these results demonstrate that the GAPDH-based vaccine is safe and stable and protects susceptible and diabetic adult mice against GBS infections. It is therefore a promising candidate as a global vaccine to prevent GBS-induced neonatal and adult diseases. Public Library of Science 2015-12-16 /pmc/articles/PMC4682941/ /pubmed/26673420 http://dx.doi.org/10.1371/journal.pone.0144196 Text en © 2015 Alves et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Alves, Joana Madureira, Pedro Baltazar, Maria Teresa Barros, Leandro Oliveira, Liliana Dinis-Oliveira, Ricardo Jorge Andrade, Elva Bonifácio Ribeiro, Adília Vieira, Luís Mira Trieu-Cuot, Patrick Duarte, José Alberto Carvalho, Félix Ferreira, Paula A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice |
title | A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice |
title_full | A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice |
title_fullStr | A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice |
title_full_unstemmed | A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice |
title_short | A Safe and Stable Neonatal Vaccine Targeting GAPDH Confers Protection against Group B Streptococcus Infections in Adult Susceptible Mice |
title_sort | safe and stable neonatal vaccine targeting gapdh confers protection against group b streptococcus infections in adult susceptible mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682941/ https://www.ncbi.nlm.nih.gov/pubmed/26673420 http://dx.doi.org/10.1371/journal.pone.0144196 |
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